Circadian rhythms in disaccharidases of rat small intestine and its relation to food intake.

The activities of maltase and sucrase of the small intestine were low at night and high in the daytime in rats which had been fed from 09.00 h to 15.00 h for 2 weeks. A remarkable rise of enzyme activities was observed at 08.00 h, 1 h before the start of feeding. The rhythmic changes in disaccharidase activities continued for at least 2 days after starvation, but completely disappeared after 5 days of starvation. It was suggested that the disaccharidase rhythms are not a direct consequence of food intake, but that anticipation of food intake acts as a trigger for initiation of the disaccharidase rhythms.     

Ammonia production by the small intestine of the rat.

1. Slices of duodenum and jejunum produce ammonia from glutamine in vitro. 2. Ammoniagenesis does not increase in response to acidosis or potassium deficiency, two conditions known to cause enhanced ammoniagenesis in the kidney. 3. Gut contains glutaminase 1 as well as gamma-glutamyl transpeptidase. 4. These enzymes do not show any increase during starvation.     

Mechanism of oleoylethanolamide on fatty acid uptake in small intestine after food intake and body weight reduction

The increase in the prevalence of human obesity highlights the need to identify molecular and cellular mechanisms involved in control of feeding and energy balance. Oleoylethanolamide (OEA), an endogenous lipid produced primarily in the small intestine, has been identified to play an important role in the regulation of animal food intake and body weight. Previous studies indicated that OEA activates peroxisome proliferator-activated receptor-alpha, which is required to mediate the effects of appetite suppression, reduces blood lipid levels, and enhances peripheral fatty acid catabolism. However, the effect of OEA on enterocyte function is unclear. In this study, we have examined the effect of OEA on intestinal fatty acid uptake and FAT/CD36 expression in vivo and in vitro. We intraperitoneally administered OEA to rats and examined FAT/CD36 mRNA level and fatty acid uptake in enterocytes isolated from the proximal small intestine, as well as in adipocytes. Our results indicate that OEA treatment significantly increased FAT/CD36 mRNA expression in intestinal mucosa and isolated jejunal enterocytes. In addition, we also found that OEA treatment significantly increases fatty acid uptake in isolated enterocytes in vitro. These results suggest that in addition to appetite regulation, OEA may regulate body weight by altered peripheral lipid metabolism, including increased lipolysis in adipocytes and enhanced fatty acid uptake in enterocytes, both in conjunction with increased expression of FAT/CD36. This study may have important implications in understanding the mechanism of OEA in the regulation of fatty acid absorption in human physiological and pathophysiological conditions.     

The morphometry and biomechanical properties of the rat small intestine after systemic treatment with epidermal growth factor

Morphometric and passive biomechanical properties were studied in isolated segments of the duodenum, jejunum and ileum in 22 EGF-treated rats and 12 control rats. The rats were allocated to groups with EGF treatment for 2, 4, 7, and 14 days (n = 6 for each EGF treatment group except n = 4 for the 14 days group) or saline treatment (n = 3 for each group). The intestinal segments were pressurized with Krebs solution from 0 to 8 cmH2O for duodenum and 0 to 6 cmH2O for jejunum and ileum using a ramp distension protocol. The diameter and length were recorded at different pressure levels. Circumferential and longitudinal stresses (force per area) and strains (deformation) were computed from the length, diameter, pressure and the zero-stress state data. EGF treatment was associated with pronounced morphometric changes, e.g., the wall thickness, wall area, and the circumferential lengths significantly increased during EGF treatment in all intestinal segments (P < 0.05). Histological analysis showed that the thickness and area of the layers increased after EGF treatment. With respect to the biomechanical data, the opening angle increased in all segments during EGF treatment with the highest value in the 14 days EGF treatment group (P < 0.05). The same result was found for residual strain and the residual strain gradient through the intestinal wall. Linear regression analysis demonstrated that the opening angle mainly depended on the mucosa thickness and area. Furthermore, the circumferential stiffness increased in the duodenum and decreased in the jejunum and ileum during EGF treatment. A plateau was reached after 7 days where after it started to normalize (P < 0.01). In the longitudinal direction, all intestinal segments became stiffer after EGF treatment for 7 days. After 14 days the curve started to normalize in duodenum and jejunum but not in the ileum.     

Intestinal kallikrein activity is reduced in a bypassed segment of the small intestine in the rat

The possible pancreatic origin of intestinal kallikrein was studied in a jejuno-ileal bypass model in the rat. The bypassed loops were made of variable lengths (2-72 cm) and samples were taken at 10 cm intervals to relate enzyme activities to adaptive changes caused by local and systemic stimulus. The kallikrein activity was dramatically reduced (mean 92.3%) in the bypassed loops while only moderately reduced (mean 35.8%) activities were found in the intestine remaining in continuity. Kallikrein was uniformly distributed throughout the functional small intestine in normal and bypass operated animals. The longitudinal distribution profiles obtained for brush border enzymes in normal animals were almost absent in the bypassed loops, but were apparent in the remaining intestine. The main adaptive growth was observed in the remaining small intestine, Both here and in the loop, the growth depended on the amount of bypassed tissue. Our observations are strongly in favour of a pancreatic origin of the glandular kallikrein activity found in the small intestine in the rat.     

Inhibition of food intake in the rat

The effects of single oral administrations of tricyclic antidepressants (imipramine and desipramine), an atypical antidepressant (nomifensine), known anorexic agents, haloperidol, and diazepam on food intake were compared in Sprague-Dawley rats over a 4-day test period. The tricyclic antidepressants produced decreases in food intake during the total 4-day test period following their administration. In contrast, the anorexic agents (d-amphetamine, cocaine, mazindol, fenfluramine and quipazine), nomifensine, and haloperidol produced decreases in food intake only on the day of their administration. Diazepam produced an increase in food intake only on the day of its administration. In addition to revealing that high doses of antidepressants can decrease food intake, this model appears to show some specificity for tricyclic antidepressants.     

Kinetic parameters of maltose hydrolysis and glucose intake in the rat small intestine in a chronic experiment

"True" (corrected for the influence of the pre-epithelial layer) kinetic constants of maltose hydrolysis (Km and Vmax) and Glucose active transport (Kt and Jmax) in the isolated loop of the rat small intestine in chronic experiments were determined using a new mathematical approach. The Km (4.260.25 mM) does not differ from that, obtained in in vitro experiments on the homogenates of mucous membrane taken from the same intestinal loops, and the Vmax (0.72 +/- 0.07 mol/(min.cm)) is 1.7 times lower than that in in vitro experiments. The Kt and Jmax values are 3.18 +/- 0.68 mM and 0.73 +/- 0.07 mol/(min.cm), resp. The estimated values of Km, Kt and Vmax are in accordance with the corresponding published data, whereas the Jmax is several times higher than the value generally believed on the basis of acute experiments in vivo. A high level of glucose absorption in the small intestine of unanesthetized animals is achieved mainly due to a high permeability of the pre-epithelial layer and a high capacity of the active transport as a major mechanism of glucose absorption in the small intestine under normal conditions.     

Slow-waves in rat small intestine

Rat small intestine generates rhythmic slow-wave activity. The slow-waves are not eliminated by ouabain application or incubation in potassium free solution. Exposure to low sodium or calcium free solution decreases slow-wave activity. Incubation in sodium and calcium free solution eliminates activity. It is concluded that rat small intestinal slow-waves may not result from the same mechanism as in the cat.     

Structure and permeability of goblet cell tight junctions in rat small intestine

Summary Two major cell types, goblet and absorptive cells, dominate the epithelial lining of small intestinal villi. We used freezefracture replicas of rat ileal mucosa to examine the possibility that tight junction structure, known to relate to transepithelial resistance, might vary with cell type. Tight junctions between absorptive cells were uniform in structure while those associated with villus goblet cells displayed structural variability. In 23% of villus goblet cell tight junctions the strand count was less than 4 and in 30% the depth was less than 200 nm. In contrast, only 4% of absorptive cell tight junctions had less than 4 strands and only 9% had depth measurements less than 200 nm. Other structural features commonly associated with villus goblet cell tight junctions but less commonly with absorptive cell tight junctions were: deficient strand cross-linking, free-ending abluminal strands, and highly fragmented strands. Bothin vivo ileal segments and everted loops were exposed to ionic lanthanum. Dense lanthanum precipitates in tight junctions and paracellular spaces were restricted to a subpopulation of villus goblet cells and were not found between villus absorptive cells. After exposure of prefixed ileal loops to lanthanum for 1 hour, faint precipitates of lanthanum were found in 14% of tight junctions and paracellular spaces between absorptive cells compared to 42% of tight junctions and paracellular spaces adjacent to villus goblet cells. When tested in Ussing chambers, the methods used for lanthanum exposure did not lower transepithelial resistance. Everted loops exposed to ionic barium and examined by light microscopy showed dense barium precipitates in the junctional zone and region of the paracellular space of villus goblet cells but not in these regions between absorptive cells. However, the macromolecular tracers, microperoxidase, cytochromec and horseradish peroxidase, were excluded from both villus goblet cell and absorptive cell paracellular spaces inin vivo segments. These findings suggest that a subpopulation of villus goblet cells may serve as focal sites of high ionic permeability and contribute to the relatively low resistance to ionic flow which characterizes the small intestinal epithelium.     

Endothelin-1 induces mucosal mast cell degranulation in the rat small intestine

The enhanced production of endothelial cell-derived vasoactive mediators and the activation of mast cells (MCs) have been implicated in the pathogenesis of mucosal damage during ischemia and reperfusion injuries. The first objective of our study was to define the in vivo relation between endothelin-1 (ET-1) and the MC system. Secondly, we determined whether pretreatment with ET receptor antagonists would attenuate MC responses to exogenous ET-1. In the first series of experiments, increasing doses of ET-1 (0. 1, 1 and 3 nmol/kg i.v.) were administered to anesthetized rats. In the second series, the animals were pretreated with equimolar doses of the ET-A receptor antagonist BQ-610 or ETR-P1/fl peptide, and the ET-B receptor antagonist IRL-1038. Intestinal perfusion changes and macrohemodynamics were recorded, and the proportion of degranulated MCs was determined in ileal biopsies. The average mucosal thickness was recorded with an image analysis system. ET-1 induced dose-dependent alterations in the hemodynamic and morphological parameters and caused pronounced mucosal injury, with a significant reduction in villus height. The ratio of degranulated MCs was similar in all ET-treated groups (77%, 82% and 86%) to that observed in animals subjected to 15-min ischemia and 60-min reperfusion (85% degranulation). Pretreatment with BQ-610 and ETR-P1/fl peptide attenuated the ET-1 induced alterations in the hemodynamic parameters and decreased structural injury to the mucosa. ET-induced MC degranulation was significantly inhibited by the ET-A receptor antagonists, but not by IRL-1038. These results indicate that elevated levels of circulating ET-1 might induce intestinal mucosal tissue injury and MC degranulation via activation of ET-A receptors, and raise the possibility that ET-A receptor antagonist administration could exert a potentially beneficial effect through a mechanism other than the blockade of vasoconstriction in pathologies associated with an increased ET-1 release.     

Effects of somatostatin on food intake in rats

We examined the possibility that somatostatin, a tetradecapeptide distributed in the gut and the central nervous system, may influence food intake and behavior in rats. Although intravenously infused somatostatin did not alter food intake in 8 hour fasted rats, intracerebroventricularly infused somatostatin resulted in a biphasic response, first increasing then decreasing food intake. We also observed that the effects of somatostatin vary depending upon whether animals are fed or fasted. In fed rats, food intake was decreased, while in fasted rats food intake was increased. These results suggest that somatostatin can act in the central nervous system to stimulate appetite; but that other factors, possibly related to gut motility or clearance, may inhibit further feeding once the stomach is full.